Variable Molecular Weight Polymer Nanoparticles for Detection and Hyperthermia-Induced Chemotherapy of Colorectal Cancer

Oxaliplatin plays a significant role as a chemotherapeutic agent for the treatment of colorectal cancer (CRC); however, oxaliplatin-resistant phenotypes make further treatment challenging. Here, we have demonstrated that rapid (60 s) hyperthermia (42 °C), generated by the near-infrared stimulation of variable molecular weight nanoparticles (VMWNPs), increases the effectiveness of oxaliplatin in the oxaliplatin-resistant CRC cells. VMWNP-induced hyperthermia resulted in a higher cell death in comparison to cells exposed to chemotherapy at 42 °C for 2 h. Fluorescence from VMWNPs was observed inside cells, which allows for the detection of CRC. The work further demonstrates that the intracellular thermal dose can be determined using cell luminescence and correlated with the cell viability and response to VMWNP-induced chemotherapy. Mild heating makes oxaliplatin-resistant cancer cells responsive to chemotherapy, and the VMWNPs-induced hyperthermia can induce cell death in a few minutes, compared to classical bulk heating. The results presented here lay the foundation for photothermal polymer nanoparticles to be used for cell ablation and augmenting chemotherapy in drug-resistant colorectal cancer cells.

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Cytotoxicity and Apoptosis Effects of Curcumin Analogue (2E,6E)-2,6-Bis(2,3-Dimethoxybenzylidine) Cyclohexanone (DMCH) on Human Colon Cancer Cells HT29 and SW620 In Vitro

Molecules ◽

10.3390/molecules26051261 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1261

Author(s):

Nurul Fattin Che Rahim ◽

Yazmin Hussin ◽

Muhammad Nazirul Mubin Aziz ◽

Nurul Elyani Mohamad ◽

Swee Keong Yeap ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Death ◽

Cancer Cells ◽

Cell Lines ◽

Curcuma Longa ◽

Metastatic Colon Cancer ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Sw620 Cell

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012–2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells.

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Bioactivity of PEGylated Graphene Oxide Nanoparticles Combined with Near-Infrared Laser Irradiation Studied in Colorectal Carcinoma Cells

Nanomaterials ◽

10.3390/nano11113061 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3061

Author(s):

Natalia Krasteva ◽

Dessislava Staneva ◽

Bela Vasileva ◽

George Miloshev ◽

Milena Georgieva

Keyword(s):

Colorectal Cancer ◽

Graphene Oxide ◽

Colorectal Carcinoma ◽

Cancer Cells ◽

Laser Irradiation ◽

Molecular Mechanisms ◽

Near Infrared ◽

Carcinoma Cells ◽

Infrared Light ◽

Mitochondrial Activity

Central focus in modern anticancer nanosystems is given to certain types of nanomaterials such as graphene oxide (GO). Its functionalization with polyethylene glycol (PEG) demonstrates high delivery efficiency and controllable release of proteins, bioimaging agents, chemotherapeutics and anticancer drugs. GO–PEG has a good biological safety profile, exhibits high NIR absorbance and capacity in photothermal treatment. To investigate the bioactivity of PEGylated GO NPs in combination with NIR irradiation on colorectal cancer cells we conducted experiments that aim to reveal the molecular mechanisms of action of this nanocarrier, combined with near-infrared light (NIR) on the high invasive Colon26 and the low invasive HT29 colon cancer cell lines. During reaching cancer cells the phototoxicity of GO–PEG is modulated by NIR laser irradiation. We observed that PEGylation of GO nanoparticles has well-pronounced biocompatibility toward colorectal carcinoma cells, besides their different malignant potential and treatment times. This biocompatibility is potentiated when GO–PEG treatment is combined with NIR irradiation, especially for cells cultured and treated for 24 h. The tested bioactivity of GO–PEG in combination with NIR irradiation induced little to no damages in DNA and did not influence the mitochondrial activity. Our findings demonstrate the potential of GO–PEG-based photoactivity as a nanosystem for colorectal cancer treatment.

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Assessment of TRPV4 Channel and Its Role in Colorectal Cancer Cells

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1683 ◽

2019 ◽

Vol 12 (2) ◽

pp. 629-638

Author(s):

N. N. Bahari ◽

S. Y. N. Jamaludin ◽

A. H. Jahidin ◽

M. N. Zahary ◽

A. B. Mohd Hilmi

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cell Death ◽

Cancer Cells ◽

Human Colorectal Cancer ◽

Expression Levels ◽

Pharmacological Modulation ◽

Colorectal Cancer Cells ◽

Ht 29

The transient receptor potential vanilloid member 4 (TRPV4) is a non-selective calcium (Ca2+)-permeable channel which is widely expressed in different types of tissues including the lungs, liver, kidneys and salivary gland. TRPV4 has been shown to serve as a cellular sensor where it is involved in processes such as osmoregulation, cell volume regulation and thermoregulation. Emerging evidence suggests that TRPV4 also plays important roles in several aspects of cancer progression. Despite the reported roles of TRPV4 in several forms of cancers, the role of TRPV4 in human colorectal cancer remains largely unexplored. In the present study, we sought to establish the potential role of TRPV4 in colorectal cancer by assessing TRPV4 expression levels and investigating whether TRPV4 pharmacological modulation may alter cell proliferation, cell cycle and cell death in colorectal cancer cells. Quantitative real-time PCR analysis revealed that TRPV4 mRNA levels were significantly lower in HT-29 cells than normal colon CCD-18Co cells. However, TRPV4 mRNA was absent in HCT-116 cells. Pharmacological activation of TRPV4 with GSK1016790A significantly enhanced the proliferation of HT-29 cells while TRPV4 inhibition using RN 1734 decreased their proliferation. Increased proliferation in GSK1016790A-treated HT-29 cells was attenuated by co-treatment with RN 1734. Pharmacological modulation of TRPV4 had no effect on the cell cycle progression but promoted cell death in HT-29 cells. Taken together, these findings suggest differential TRPV4 expression levels in human colorectal cancer cells and that pharmacological modulation of TRPV4 produces distinct effects on the proliferation and induces cell death in HT-29 cells.

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p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21239315 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9315

Author(s):

Eun Joo Jung ◽

Won Sup Lee ◽

Anjugam Paramanantham ◽

Hye Jung Kim ◽

Sung Chul Shin ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Cancer Cells ◽

Artemisia Annua ◽

Flow Cytometric Analysis ◽

Lamin A ◽

Artemisia Annua L ◽

Anticancer Effects ◽

Colorectal Cancer Cells ◽

Hct116 Cells

Plant-derived natural polyphenols exhibit anticancer activity without showing any noticeable toxicities to normal cells. The aim of this study was to investigate the role of p53 on the anticancer effect of polyphenols isolated from Korean Artemisia annua L. (pKAL) in HCT116 human colorectal cancer cells. We confirmed that pKAL induced reactive oxygen species (ROS) production, propidium iodide (PI) uptake, nuclear structure change, and acidic vesicles in a p53-independent manner in p53-null HCT116 cells through fluorescence microscopy analysis of DCF/PI-, DAPI-, and AO-stained cells. The pKAL-induced anticancer effects were found to be significantly higher in p53-wild HCT116 cells than in p53-null by hematoxylin staining, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/PI-stained cells. In addition, expression of ectopic p53 in p53-null cells was upregulated by pKAL in both the nucleus and cytoplasm, increasing pKAL-induced cell death. Moreover, Western bot analysis revealed that pKAL-induced cell death was associated with upregulation of p53-dependent targets such as p21, Bax and DR5 and cleavage of PARP1 and lamin A/C in p53-wild HCT116 cells, but not in p53-null. Taken together, these results indicate that p53 plays an important role in enhancing the anticancer effects of pKAL by upregulating p53 downstream targets and inducing intracellular cell death processes.

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Selective Suppression of Cell Growth and Programmed Cell Death-Ligand 1 Expression in HT1080 Fibrosarcoma Cells by Low Molecular Weight Fucoidan Extract

Marine Drugs ◽

10.3390/md17070421 ◽

2019 ◽

Vol 17 (7) ◽

pp. 421 ◽

Cited By ~ 3

Author(s):

Kiichiro Teruya ◽

Yoshihiro Kusumoto ◽

Hiroshi Eto ◽

Noboru Nakamichi ◽

Sanetaka Shirahata

Keyword(s):

Molecular Weight ◽

Cell Death ◽

Programmed Cell Death ◽

Cancer Cells ◽

Biological Activities ◽

Immune Surveillance ◽

Selective Inhibition ◽

Low Molecular Weight ◽

Fibrosarcoma Cells ◽

Self Protection

Low molecular weight fucoidan extract (LMF), prepared by an abalone glycosidase digestion of a crude fucoidan extracted from Cladosiphon novae-caledoniae Kylin, exhibits various biological activities, including anticancer effect. Various cancers express programmed cell death-ligand 1 (PD-L1), which is known to play a significant role in evasion of the host immune surveillance system. PD-L1 is also expressed in many types of normal cells for self-protection. Previous research has revealed that selective inhibition of PD-L1 expressed in cancer cells is critical for successful cancer eradication. In the present study, we analyzed whether LMF could regulate PD-L1 expression in HT1080 fibrosarcoma cells. Our results demonstrated that LMF suppressed PD-L1/PD-L2 expression and the growth of HT1080 cancer cells and had no effect on the growth of normal TIG-1 cells. Thus, LMF differentially regulates PD-L1 expression in normal and cancer cells and could serve as an alternative complementary agent for treatment of cancers with high PD-L1 expression.

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Abstract 1692:KRAS-mediated therapeutic resistance abrogates immunogenic cell death in colorectal cancer cells

10.1158/1538-7445.am2017-1692 ◽

2017 ◽

Author(s):

Yi-Jun Wang ◽

Dongshi Chen ◽

Jingshan Tong ◽

Jian Yu ◽

Alberto Bardelli ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Cancer Cells ◽

Therapeutic Resistance ◽

Immunogenic Cell Death ◽

Colorectal Cancer Cells

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Sourcing the immune system to induce immunogenic cell death in Kras-colorectal cancer cells

British Journal of Cancer ◽

10.1038/s41416-019-0561-z ◽

2019 ◽

Vol 121 (9) ◽

pp. 768-775

Author(s):

Mara Cirone ◽

Lavinia Vittoria Lotti ◽

Marisa Granato ◽

Livia Di Renzo ◽

Ida Biunno ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Cancer Cells ◽

Cell Activation ◽

Cytotoxic T Cells ◽

Single Agent ◽

Atp Release ◽

Immunogenic Cell Death ◽

Dendritic Cell Activation ◽

Colorectal Cancer Cells

Abstract Background Current approaches aimed at inducing immunogenic cell death (ICD) to incite an immune response against cancer neoantigens are based on the use of chemotherapeutics and other agents. Results are hampered by issues of efficacy, combinatorial approaches, dosing and toxicity. Here, we adopted a strategy based on the use of an immunomolecule that overcomes pharmachemical limitations. Methods Cytofluorometry, electron microscopy, RT-PCR, western blotting, apotome immunofluorescence, MLR and xenografts. Results We report that an ICD process can be activated without the use of pharmacological compounds. We show that in Kras-mut/TP53-mut colorectal cancer cells the 15 kDa βGBP cytokine, a T cell effector with onco-suppressor properties and a potential role in cancer immunosurveillance, induces key canonical events required for ICD induction. We document ER stress, autophagy that extends from cancer cells to the corresponding xenograft tumours, CRT cell surface shifting, ATP release and evidence of dendritic cell activation, a process required for priming cytotoxic T cells into a specific anticancer immunogenic response. Conclusions Our findings provide experimental evidence for a rationale to explore a strategy based on the use of an immunomolecule that as a single agent couples oncosuppression with the activation of procedures necessary for the induction of long term response to cancer.

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